Sunday, August 21, 2011

How Does Something Get into a Textbook?

A recent paper in Molecular Cell involved the study of nucleosome assembly in vitro (Torigoe et al. 2011). The authors were looking for intermediate stages in the assembly of nucleosome after DNA replication. Here's the abstract of their paper ...

Chromatin assembly involves the combined action of histone chaperones and ATP-dependent motor proteins. Here, we investigate the mechanism of nucleosome assembly with a purified chromatin assembly system containing the histone chaperone NAP1 and the ATP-dependent motor protein ACF. These studies revealed the rapid formation of a stable nonnucleosomal histone-DNA intermediate that is converted into canonical nucleosomes by ACF. The histone-DNA intermediate does not supercoil DNA like a canonical nucleosome, but has a nucleosome-like appearance by atomic force microscopy. This intermediate contains all four core histones, lacks NAP1, and is formed by the initial deposition of histones H3-H4. Conversion of the intermediate into histone H1-containing chromatin results in increased resistance to micrococcal nuclease digestion. These findings suggest that the histone-DNA intermediate corresponds to nascent nucleosome-like structures, such as those observed at DNA replication forks. Related complexes might be formed during other chromatin-directed processes such as transcription, DNA repair, and histone exchange.

Interesting but hardly Earth-shattering. More work needs to be done to confirm this result and see if it's significant in vivo. At least that's what you would think if you just looked at the paper.

Basic biology textbooks may need a bit of revising now that biologists at UC San Diego have discovered a never-before-noticed component of our basic genetic material.

According to the textbooks, chromatin, the natural state of DNA in the cell, is made up of nucleosomes. And nucleosomes are the basic repeating unit of chromatin.

That's correct. All the textbooks have a diagram similar to the one shown here from my textbook. It shows the organization of nucleosome core particles and the completed nucleosome on DNA.

What the new result shows is that there's an intermediate stage where the core particle is bound to DNA but the DNA isn't wrapped around the core particle. That's not a big surprise and it's not going to make it into most textbooks, even if it's true.

"This novel particle was found as a precursor to a nucleosome," said James Kadonaga, a professor of biology at UC San Diego who headed the research team and calls the particle a "pre-nucleosome." "These findings suggest that it is necessary to reconsider what chromatin is. The pre-nucleosome is likely to be an important player in how our genetic material is duplicated and used."

The biologists say that while the pre-nucleosome may look something like a nucleosome under the microscope, biochemical tests have shown that it is in reality halfway between DNA and a nucleosome.

These pre-nucleosomes, the researchers say, are converted into nucleosomes by a motor protein that uses the energy molecule ATP.

"The discovery of pre-nucleosomes suggests that much of chromatin, which has been generally presumed to consist only of nucleosomes, may be a mixture of nucleosomes and pre-nucleosomes," said Kadonaga. "So, this discovery may be the beginning of a revolution in our understanding of what chromatin is."

This is mostly hype and none of this speculation is found in the actual paper. Unfortunately, this sort of press release has become the norm and that's got to stop.

This work isn't even close to making into the textbooks for a number of reasons. The most obvious is that it needs to be confirmed. Textbook writers do not immediately put new findings into their books because we've been burned too many times. But there's another reason why this ain't gonna make it—it's not important enough.

Textbooks are not encyclopedias. They will only contain information that undergraduates need to know in order to understand the basic concepts and principles in the field. I know that every scientist thinks his or her most recent discovery is Nobel Prize work and I'm sure they would like every biochemistry undergraduate to know about it. At some point a textbook author has to decide what's really important and, unfortunately, those choices mean that 99.99% of everything that's published in a given year doesn't make the cut.

4 comments
:

As a fledgling textbook writer, I'm curious about your decisions about what goes into a new edition and what doesn't. I find that adding in relatively recent research is a good way to breathe new life into a subject. Rather than stick with examples of evolution form the 1950s, I can look at all sorts of recent studies that can integrate natural history with genomics, etc., because scientists have many more tools at hand. I think this strategy can make a subject more interesting to students, because they can see how the science is rolling along even today--it didn't stop in 1950.

On the other hand, I have written about really new papers that reviewers later flagged as being less impressive than they might appear. So I am finding it a tricky balancing act. What are your criteria?

I focus on fundamental principles and concepts. That's the stuff students need to know. If a recently published result enhances one of those concepts, or provides an interesting example, then I'll consider putting it into my book.

Since my book is an introductory biochemistry textbook I'm not really interested in the latest results at the front line of the field. It's very rare that anything published in the recent literature will change the good old-fashioned basic concepts that students need to know.

But here's the problem. The instructors who use the textbook are often researchers and they would dearly love to think that beginning undergraduates will be as excited as they are about the latest paper in Science or Nature.

That's just not true. In order to understand and appreciate those papers the students will have to learn a lot of basic stuff first. We need to make that basic stuff as interesting—and as accurate—as possible and we're not doing our students any favors by sacrificing the basics for the glamor.

It's very frustrating because some intructors won't use my book because we don't have a whole chapter on "signal transduction" or "systems biology" or "cancer", or "bioinformatics."

I appreciate a mix of older classic examples in my textbooks, and some newer spins to try and give students a notion of what the frontier looks like.

When it comes to something more involved and specialized, I think that is best approached based on the individual instructors territory. I believe students benefit, by some of the excitement, interest, and detail that you can deliver when talking about your field. The trick of course is that you can't really put that into the textbook for other people outside your field.

not curious or interested in the evolution of chromatin? be critical of the mainstream encrusted tenured bioideology, it's only there to guide imagination, so some silly idea as a precursor to chromatin can open a door that suggests how far we need to go

Laurence A. Moran

Larry Moran is a Professor Emeritus in the Department of Biochemistry at the University of Toronto. You can contact him by looking up his email address on the University of Toronto website.

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Quotations

The old argument of design in nature, as given by Paley, which formerly seemed to me to be so conclusive, fails, now that the law of natural selection has been discovered. We can no longer argue that, for instance, the beautiful hinge of a bivalve shell must have been made by an intelligent being, like the hinge of a door by man. There seems to be no more design in the variability of organic beings and in the action of natural selection, than in the course which the wind blows.Charles Darwin (c1880)Although I am fully convinced of the truth of the views given in this volume, I by no means expect to convince experienced naturalists whose minds are stocked with a multitude of facts all viewed, during a long course of years, from a point of view directly opposite to mine. It is so easy to hide our ignorance under such expressions as "plan of creation," "unity of design," etc., and to think that we give an explanation when we only restate a fact. Any one whose disposition leads him to attach more weight to unexplained difficulties than to the explanation of a certain number of facts will certainly reject the theory.

Charles Darwin (1859)Science reveals where religion conceals. Where religion purports to explain, it actually resorts to tautology. To assert that "God did it" is no more than an admission of ignorance dressed deceitfully as an explanation...

Quotations

The world is not inhabited exclusively by fools, and when a subject arouses intense interest, as this one has, something other than semantics is usually at stake.
Stephen Jay Gould (1982)
I have championed contingency, and will continue to do so, because its large realm and legitimate claims have been so poorly attended by evolutionary scientists who cannot discern the beat of this different drummer while their brains and ears remain tuned to only the sounds of general theory.
Stephen Jay Gould (2002) p.1339
The essence of Darwinism lies in its claim that natural selection creates the fit. Variation is ubiquitous and random in direction. It supplies raw material only. Natural selection directs the course of evolutionary change.
Stephen Jay Gould (1977)
Rudyard Kipling asked how the leopard got its spots, the rhino its wrinkled skin. He called his answers "just-so stories." When evolutionists try to explain form and behavior, they also tell just-so stories—and the agent is natural selection. Virtuosity in invention replaces testability as the criterion for acceptance.
Stephen Jay Gould (1980)
Since 'change of gene frequencies in populations' is the 'official' definition of evolution, randomness has transgressed Darwin's border and asserted itself as an agent of evolutionary change.
Stephen Jay Gould (1983) p.335
The first commandment for all versions of NOMA might be summarized by stating: "Thou shalt not mix the magisteria by claiming that God directly ordains important events in the history of nature by special interference knowable only through revelation and not accessible to science." In common parlance, we refer to such special interference as "miracle"—operationally defined as a unique and temporary suspension of natural law to reorder the facts of nature by divine fiat.
Stephen Jay Gould (1999) p.84

Quotations

My own view is that conclusions about the evolution of human behavior should be based on research at least as rigorous as that used in studying nonhuman animals. And if you read the animal behavior journals, you'll see that this requirement sets the bar pretty high, so that many assertions about evolutionary psychology sink without a trace.

Jerry Coyne
Why Evolution Is TrueI once made the remark that two things disappeared in 1990: one was communism, the other was biochemistry and that only one of them should be allowed to come back.

Sydney Brenner
TIBS Dec. 2000
It is naïve to think that if a species' environment changes the species must adapt or else become extinct.... Just as a changed environment need not set in motion selection for new adaptations, new adaptations may evolve in an unchanging environment if new mutations arise that are superior to any pre-existing variations

Douglas Futuyma
One of the most frightening things in the Western world, and in this country in particular, is the number of people who believe in things that are scientifically false. If someone tells me that the earth is less than 10,000 years old, in my opinion he should see a psychiatrist.

Francis Crick
There will be no difficulty in computers being adapted to biology. There will be luddites. But they will be buried.

Sydney Brenner
An atheist before Darwin could have said, following Hume: 'I have no explanation for complex biological design. All I know is that God isn't a good explanation, so we must wait and hope that somebody comes up with a better one.' I can't help feeling that such a position, though logically sound, would have left one feeling pretty unsatisfied, and that although atheism might have been logically tenable before Darwin, Darwin made it possible to be an intellectually fulfilled atheist

Richard Dawkins
Another curious aspect of the theory of evolution is that everybody thinks he understand it. I mean philosophers, social scientists, and so on. While in fact very few people understand it, actually as it stands, even as it stood when Darwin expressed it, and even less as we now may be able to understand it in biology.

Jacques Monod
The false view of evolution as a process of global optimizing has been applied literally by engineers who, taken in by a mistaken metaphor, have attempted to find globally optimal solutions to design problems by writing programs that model evolution by natural selection.